Kidney Injury in Patients with Acute Decompensated Heart Failure

摘要 急性失代偿性心力衰竭(ADHF)住院是一个重大的公共卫生问题， 代表一个前哨预后事件，在治疗期间和治疗后临床结局不良的风险很高。 住院治疗。调查改善ADHF患者的护理是公共卫生的优先事项。肾脏 在ADHF的急性治疗和预后中起核心作用。肾损伤在中国非常普遍 ADHF是血液动力学改变、神经激素失调和氧化应激的顶峰 导致肾内皮细胞损伤、炎症和缺血性损伤。肾脏损伤也是一个关键 在标准AHDF治疗的开始和停止的决定中的组成部分，这最终影响 ADHF的临床预后。然而，对肾脏损伤的系统测量和考虑并不是 纳入ADHF疗法的算法，可能是由于目前临床可用的肾脏的限制 伤害措施。血清肌酐传统上被用来确定ADHF患者的肾脏损害，然而 对正在进行的肾脏损伤或修复反应迟缓且变化缓慢；这限制了其在动态中的使用 如ADHF等条件。研究表明，血清肌酐与系统性红斑狼疮 ADHF患者无充血或短期预后。因此，当前的ADHF指南不支持序列 测定血清肌酐。这项提议的目标是识别新的肾脏损伤标记物， 指导治疗，更好地判断ADHF的预后；从而改善住院和长期结果。 为了解决这一知识差距，我们建议对ADHF患者进行一项大型前瞻性研究，以 确定：(1)新的肾脏损伤标记物的系统、连续测量是否随 标准化的循证ADHF治疗方案；(2)以及这些变化是否与 患者报告的、住院期间和长期结果。基于以前的文献，我们选择研究一种 一组新的肾脏损伤措施，包括内皮损伤、炎症、肾小管应激/损伤，这些可能 更好地反映肾脏内的病理生理，与之相比，可能更动态地反映肾脏的损伤/修复 与血清肌酐有关。这些新的肾脏损伤措施有望在近期投入临床使用。 然而，未来在ADHF中的研究还不是很好。为了支持我们的假设，我们进行了一项试验 对62例ADHF患者的研究发现，新的肾脏损伤措施显示出更大的 对标准化ADHF治疗反应的相对变化与全身充血有很好的相关性； 而血清肌酐相对稳定，与全身性充血相关性较差。这 前景看好的试点数据支持了拟议工作的科学基础和可行性。数据 这项研究将被用来确定ADHF患者中最有希望的肾脏损伤标志物，并可能 未来机制研究或临床试验的基础，以测试ADHF治疗策略 新的肾脏损伤标志物。

ABSTRACT Hospitalization for acute decompensated heart failure (ADHF) is a significant public health issue and represents a sentinel prognostic event, with high risk of poor clinical outcomes during and after the hospitalization. Investigation to improve the care of ADHF patients is a public health priority. The kidneys have a central role in the acute management and prognosis of ADHF. Kidney injury is highly prevalent in ADHF and is the culmination of hemodynamic alterations, neurohormonal dysregulation, and oxidative stress which cause intra-kidney endothelial damage, inflammation and ischemic injury. Kidney injury is also a key component in decisions of initiation and withdrawal of standard AHDF therapies, which ultimately affects clinical prognosis of ADHF. However, systematic measurement and consideration of kidney injury is not incorporated into algorithms of ADHF therapies, likely due to limitations of current clinically available kidney injury measures. Serum creatinine has traditionally been used to define kidney injury in ADHF, however rises late and is slow to change in response to ongoing kidney injury or repair; which limits its use in dynamic conditions such as ADHF. Studies have shown that serum creatinine is not associated with systemic decongestion or with short-term prognosis in ADHF. Thus, current ADHF guidelines do not endorse serial measures of serum creatinine. The goal of this proposal is to identify novel kidney injury markers that can guide therapy and better determine prognosis in ADHF; thereby improve in-hospital and long-term outcomes. To address this knowledge gap, we propose to conduct a large, prospective study of ADHF patients to determine: (1) if systematic, serial measurements of novel kidney injury markers change in response to a standardized, evidence-based ADHF treatment protocol; (2) and whether these changes are associated with patient-reported, in-hospital and long-term outcomes. Based on previous literature, we have chosen to study a panel of novel kidney injury measures of endothelial injury, inflammation, tubular stress/damage which may better reflect intra-kidney pathophysiology, and may be more dynamic to reflect kidney injury/repair compared with serum creatinine. These novel kidney injury measures are poised to be clinically available in the near future, however are not well studied in ADHF. To support our hypothesis, we conducted a pilot prospective study of 62 patients admitted with ADHF and found that novel kidney injury measures demonstrated greater relative change in response to standardized ADHF therapies and correlated well with systemic congestion; while serum creatinine was relatively static and correlated poorly with systemic congestion. This promising pilot data supports the scientific rationale and feasibility of the proposed work. The data from this study will be used to identify the most promising kidney injury markers in ADHF patients and may be the foundation of future mechanistic studies or a clinical trial to test an ADHF treatment strategy guided by novel kidney injury markers.